This project is concerned with metabolic alterations in the brain which occur in experimentally-induced amino acid imbalances. Investigations are being carried out on the effects of various acute and chronic hyperaminoacidemias on processes which may be involved in the regulation of amino acid and protein metabolism in the brain. The amino acids given in excess are representative of those involved in aminoacidopathies associated with overt brain damage in human infants. The specific phenomena studied include (a) developmental and regional differences in the sensitivity of the brain to alterations in amino acid distribution resulting from amino acid loading, (b) the relationship of the resulting amino acid imbalances to variations in components of brain protein-synthesizing systems, and (c) the basic metabolic mechanisms underlying these processes.